Although it looked to be lights out for InflaRx’s C5a antibody vilobelimab in the rare skin disorder pyoderma gangrenosum (PG) last year, the German drugmaker ended 2025 with a glimmer of hope for the asset, thanks to multiple analyses of a terminated phase 3 trial.
Following the end of the late-stage study in ulcerative PG last May over futility, post hoc analyses have pointed to a “positive trend in favor of vilobelimab, with signals indicating a potentially consistent treatment effect,” InflaRx said in a Dec. 30 press release.
In turn, the company—which is broadly seeking to develop inflammatory drugs targeting the complement system—anticipates meeting with the FDA to hash out a potential development path forward for its drug in PG. InflaRx said it expects that any revamped development efforts in the indication “would only be conducted in collaboration with a partner.”
“Our in-depth data analysis reveals signals of efficacy, particularly regarding ulcer volume reduction, which further supports the potential role of the C5a/C5aR pathway in certain neutrophilic skin diseases, such as PG,” Niels Riedemann, M.D., Ph.D., InflaRx’s chief executive, said in a statement.
“Depending on the outcome of our anticipated FDA interactions, our results may provide an opportunity to advance development in collaboration with a partner, which we may pursue in the future,” he continued.
PG is a rare skin condition that causes large, painful sores to form on the skin, frequently on the legs. The exact cause of the condition isn’t fully understood, though it is believed to be an immune disorder, according to the Mayo Clinic.
For its part, vilobelimab is designed to block the activity of C5a—a fragment of the immune system’s complement cascade—and has demonstrated “high selectivity towards its targets in human blood,” InflaRx noted in its release. The company stressed that, unlike drugs designed to block C5, vilobelimab leaves the formation of the membrane attack complex intact, recognizing it as an “important defense mechanism of the innate immune system.”
Less than a year ago, InflaRx nixed its PG study of vilobelimab after an independent data monitoring committee called for the trial’s early termination, citing futility. The recommendation, which the data monitoring committee leveled after analyzing results on the first 30 patients enrolled in the trial, prompted InflaRx to declare it was stopping development of vilobelimab in the indication.
While InflaRx has no drugs with full FDA approvals, vilobelimab boasts an emergency use authorization (EUA) to treat certain critically ill COVID-19 patients. The termination of the PG study in May had no bearing on the EUA or on vilobelimab’s status in the U.S. as a COVID treatment, InflaRx clarified last year. The antibody drug is marketed under the name Gohibic in its COVID-19 niche.
As for the latest interpretation of the PG data, InflaRx said it leveraged its primary intent-to-treat analysis and several more post hoc assessments on the 54 participants enrolled in the study at the time of termination. That patient pool included 30 who had completed half a year of treatment on vilobelimab, the company pointed out.
Notably, the primary clinical endpoint of complete target ulcer closure on two consecutive visits revealed a difference favoring vilobelimab (20.8%) over placebo (16.7%), despite not being significant enough to satisfy the trial as designed, InflaRx said.
InflaRx also flagged trends favoring its drug across several key secondary endpoints in the terminated study.
For instance, nearly 30% of patients on vilobelimab achieved complete disease remission—defined by the complete closure of all ulcers—versus just 5.6% of patients in the study’s control cohort. Vilobelimab further helped 36.4% of patients reduce their ulcer volume by 50% or more at 26 weeks, compared to 16.7% of patients on placebo.
InflaRx additionally flagged further post hoc analyses that suggest “there is an overall treatment effect with vilobelimab when compared to placebo.”
The German drugmaker said it used a mixed model for repeated measures for percent change in target ulcer volume and analyses of covariance for mean of percentage changes from baseline in volume over a certain time span to further crack open the data. Those subsequent analyses yielded a “significant treatment difference” for vilobelimab over placebo from Week 14 to Week 26 of treatment and suggested vilobelimab dosing beyond 26 weeks “may provide improved treatment outcomes.”
“Unfortunately, there is not a successful precedent for conducting a pivotal Phase 3 placebo-controlled study in PG, and I believe the futility leading to early discontinuation relates to challenges in trial design rather than lack of efficacy of the therapy,” Benjamin Kaffenberger, M.D., of The Ohio State University Wexner Medical Center, said in InflaRx’s release.
“I believe that blocking C5a/C5aR in this neutrophilic disease continues to make scientific and clinical sense and that there is a strong justification to move forward,” he added.
As for what comes next, InflaRx is expecting to meet with the FDA to discuss a potential development path forward in PG, possibly through the use of alternative endpoints.
At the time of last year’s trial termination, InflaRx noted that it would focus its resources on its oral small molecule candidate izicopan, which is also a CFa inhibitor. That remains the case heading into 2026, as well.
In a bid to prioritize izicopan’s development in conditions like chronic spontaneous urticaria (CSU) and hidradenitis suppurativa (HS), the company noted that it “does not expect to deploy significant resources towards future vilobelimab development in PG on its own and will instead consider doing so in collaboration with a partner.”
Back in November, InflaRx unveiled positive phase 2a basket data on izicopan—then coded INF904—in both HS and CSU, flagging the drug’s prospects as a “potentially transformational and best-in-class immunomodulatory agent” in the indications.
Meanwhile, over the summer, InflaRx indicated that it believes CSU and HS could each represent markets of $1 billion or more for izicopan. At the time, the company noted that it had around 53.7 million euros in cash and equivalents, plus about 40.7 million euros in marketable securities. That should provide InflaRx with a cash runway stretching into 2027, InflaRx said in August.